ArticleNeuro-oncology2017
NF-κB upregulation through epigenetic silencing of LDOC1 drives tumor biology and specific immunophenotype in Group A ependymoma.
Article in Neuro-oncology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 23 citations in OpenAlex.
- TRP Channel Inhibition and NF-κB Pathway Suppression in Human Ependymal Tumor cell-line by Achillea Biebersteinii Aqueous Extract.Cell biochemistry and biophysics · 2025Article
- Loss of LDOC1 by chromatin compaction in mesenchymal tumor cells is required for PFA1 ependymoma growth.Neuro-oncology · 2025Article
- LINC01270 Regulates the NF-κB-Mediated Pro-Inflammatory Response via the miR-326/LDOC1 Axis in THP-1 Cells.Cells · 2024Article
- Multi-omic approach identifies hypoxic tumor-associated myeloid cells that drive immunobiology of high-risk pediatric ependymoma.iScience · 2023Article
- Immunobiology and Cytokine Modulation of the Pediatric Brain Tumor Microenvironment: A Scoping Review.Cancers · 2023Article
- Pro-inflammatory cytokines mediate the epithelial-to-mesenchymal-like transition of pediatric posterior fossa ependymoma.Nature communications · 2022Article
- The biology of ependymomas and emerging novel therapies.Nature reviews. Cancer · 2022Review
- Review
- Review
- Weighing ependymoma as an epigenetic disease.Journal of neuro-oncology · 2020Review
- Single-Cell RNA Sequencing of Childhood Ependymoma Reveals Neoplastic Cell Subpopulations That Impact Molecular Classification and Etiology.Cell reports · 2020Article
- Expression and Clinical Significance of Translation Regulatory Long Non-Coding RNA 1 (TRERNA1) in Ependymomas.Pathology oncology research : POR · 2020Article
- Intracranial ependymomas: molecular insights and translation to treatment.Brain pathology (Zurich, Switzerland) · 2020Review
- Discriminating Origin Tissues of Tumor Cell Lines by Methylation Signatures and Dys-Methylated Rules.Frontiers in bioengineering and biotechnology · 2020Article
- Investigation of miRNA and mRNA Co-expression Network in Ependymoma.Frontiers in bioengineering and biotechnology · 2020Article
- Establishment of patient-derived orthotopic xenograft model of 1q+ posterior fossa group A ependymoma.Neuro-oncology · 2019Article
- Genomic Landscape of Intramedullary Spinal Cord Gliomas.Scientific reports · 2019Article
- Effects of LDOC1 on colorectal cancer cells via downregulation of the Wnt/β-catenin signaling pathway.Oncology reports · 2019Article
- Specific expression of PD-L1 in RELA-fusion supratentorial ependymoma: Implications for PD-1-targeted therapy.Pediatric blood & cancer · 2018Article
- Improving Diagnostic and Therapeutic Outcomes in Pediatric Brain Tumors.Molecular diagnosis & therapy · 2018Review
Corrections and comments
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Authors and funding
17 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundInflammation has been identified as a hallmark of high-risk Group A (GpA) ependymoma (EPN). Chronic interleukin (IL)-6 secretion from GpA tumors drives an immune suppressive phenotype by polarizing infiltrating monocytes. This study determines the mechanism by which IL-6 is dysregulated in GpA EPN.
methodsTwenty pediatric GpA and 21 pediatric Group B (GpB) EPN had gene set enrichment analysis for MSigDB Hallmark gene sets performed. Protein and RNA from patients and cell lines were used to validate transcriptomic findings. GpA cell lines 811 and 928 were used for in vitro experiments performed in this study.
resultsThe nuclear factor-kappaB (NF-κB) pathway is a master regulator of IL-6 and a signaling pathway enriched in GpA compared with GpB EPN. Knockdown of NF-κB led to significant downregulation of IL-6 in 811 and 928. NF-κB activation was independent of tumor necrosis factor alpha (TNF-α) stimulation in both cell lines, suggesting that NF-κB hyperactivation is mediated through an alternative mechanism. Leucine zipper downregulated in cancer 1 (LDOC1) is a known transcriptional repressor of NF-κB. In many cancers, LDOC1 promoter is methylated, which inhibits gene transcription. We found decreased LDOC1 gene expression in GpA compared with GpB EPN, and in other pediatric brain tumors. EPN cells treated with 5AZA-DC, demethylated LDOC1 regulatory regions, upregulated LDOC1 expression, and concomitantly decreased IL-6 secretion. Stable knockdown of LDOC1 in EPN cell lines resulted in a significant increase in gene transcription of v-rel avian reticuloendotheliosis viral oncogene homolog A, which correlated to an increase in NF-κB target genes.
conclusionThese results suggest that epigenetic silencing of LDOC1 in GpA EPN regulates tumor biology and drives inflammatory immune phenotype.
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Registered trials
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